The use of glycosaminoglycans, and particularly of heparins, in anticoagulant and antithrombotic therapies is well known.
Sulodexide is a glycosaminoglycan of natural origin, extracted from mammalian intestinal mucosa, possessing a sulfation degree and an anticoagulant activity lower than those of heparin, as shown by Radhakrishnamurthy B. et at., Atherosclerosis, 31, 217-229, (1978). It is marketed under the trademark VESSEL DUE F.RTM. for the treatment of vascular pathologies with thrombotic risk like periferal arteriopathies, as shown by Crepaldi G. et al., Atherosclerosis, 81, 233, (1990), cardiovasculopathies, as shown by Tramarin R. et al., Medical Praxis, 8, 1, (1987), cerebrovasculopathies, as shown by Sozzi C., Eur. Rev. Med. Pharmacol. Sci., 6, 295, (1984) and venous pathologies of the lower limbs, as shown by Cospite M. et al., Acta Therapeutica, 18, 149, (1992).
Kanwar Y. S. et al., Sem. Nephrol., 5, 307, (1985) and Groggel G. C. et al., Kidney Int., 33, 517, (1988), recently produced evidence of the probable role of glycosaminoglycans in helping the integrity and the functioning of the renal cells.
Moreover, Canfield J. P. et at., Lab. Invest., 39, 505, (1978), previously showed a decrease of glycosaminoglycans of membrane in many conditions of nephropathy, while Baggio B. et al., Nephron., 43, 187, (1986) showed this decrease through an increased urinary elimination of glycosaminoglycans in diabetic, non-albuminuric, patients. This increased excretion of glycosaminoglycans in diabetic nephropathies, shown also by Partasarathy N. et al., Diabetes, 31, 738, (1982), recently suggested to Gambaro G. et al., Metabolism, 38, 419, (1989), the possibility of resorting to the determination of the amount of glycosaminoglycans excreted by urinary route as an analytical method more reliable than the microalbuminuria in the recognition of the nephropathy of diabetic origin.
Lastly, Diamond J. R. et al., Renal Physiol., 9, 366, (1986) and Parkerson M. B. et al, J. Clin. Invest., 81, 69, (1988), showed in animals the potential protective effect of heparin and its derivatives in models of experimental nephropathy not related to diabetic nephropathy, like chronic nephrosis from aminoglycosides and renal pathologies resulting from the subtotal renal ablation in the rat.
Lastly, the possibility to use heparin, low molecular weight heparin fractions, chemically modified heparins or low molecular weight dermatan sulfate in the treatment of the diabetic nephropathy and neuropathy has been described in the European patent publication EP 0513513. This possibility of therapeutic use was shown by means of pharmacological tests on animals: diabetes was caused by streptozotocin in Sprague Dawley male albino rats and the diabetic rats were treated with the above mentioned glycosaminoglycans whose effectiveness was determined on the basis of some parameters like the diminution of the albuminuria and of the thickness of the basal glomerular membrane and the increase of the glomerular anionic charges.